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Updated: Oct 17, 2025
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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
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Antisense oligonucleotides: absorption, distribution, metabolism, and excretion.
Mohammad Shadid1, Mohamed Badawi2, Abedelnasser Abulrob3,4
1Nonclinical Development, Sarepta Therapeutics, Inc, Cambridge, MA, USA.
Expert Opinion on Drug Metabolism & Toxicology
|October 13, 2021
Summary
Antisense oligonucleotides (ASOs) are advanced RNA-based therapeutics. This review details the absorption, distribution, metabolism, and excretion (ADME) of phosphorodiamidate morpholino oligomers (PMOs) and phosphorothioates (PSs) to guide future drug development.
Area of Science:
- RNA-based therapeutics
- Drug development
- Pharmacokinetics
Background:
- Antisense oligonucleotides (ASOs) represent a significant advancement in drug modality, with six ASO drugs approved since 2016.
- ASOs are the most developed class within RNA-based therapeutics, addressing unmet medical needs.
- The field is rapidly expanding with numerous candidates in clinical development.
Purpose of the Study:
- To review the absorption, distribution, metabolism, and excretion (ADME) properties of key ASO platforms.
- To compare the ADME profiles of phosphorodiamidate morpholino oligomers (PMOs) and phosphorothioates (PSs).
- To provide insights for the safe and innovative development of ASO drugs.
Main Methods:
- Literature review focusing on ASO platforms.
- Detailed discussion of ADME properties for PMO and PS backbones.
- Analysis of existing data on ASO pharmacokinetics.
Main Results:
- Phosphorodiamidate morpholino oligomers (PMOs) and phosphorothioates (PSs) are the predominant backbones in advanced ASO platforms.
- Comprehensive discussion of the absorption, distribution, metabolism, and excretion (ADME) characteristics for both PMO and PS platforms.
- Identification of key factors influencing ASO pharmacokinetics.
Conclusions:
- Understanding ADME properties is crucial for advancing ASO therapy.
- This knowledge facilitates the safe development and innovation of new ASO drugs.
- Further research into ADME can optimize ASO efficacy and safety profiles.
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